| Investigation of anticholinergic and non-steroidal anti-inflammatory prodrugs which reduce chemically induced skin inflammation. | |
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MedLine Citation:
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PMID: 21319177 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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As part of a continuous effort to develop efficient counter measures against sulfur mustard injuries, several unique NSAID prodrugs have been developed and screened for anti-inflammatory properties. Presented herein are three classes of prodrugs which dually target inflammation and cholinergic dysfunction. Compounds 1-28 contain common NSAIDs linked either to choline bioisosteres or to structural analogs of acetylcholinesterase (AChE) inhibitors. These agents have shown utility as anti-vesicants and anti-inflammatory agents when screened in a mouse ear vesicant model (MEVM) against both 2-chloroethyl ethyl sulfide (CEES), a blistering agent, and 12-O-tetradecanoylphorbol-13-acetate (TPA), a common topical irritant. Many of the prodrugs have activity against CEES, with 5, 18, 22 and 27 reducing inflammation by more than 75% compared with a control. Compounds 12, 13, 15 and 22 show comparable activity against TPA. Promising activity in the MEVM is related to half-lives of NSAID release in plasma, moderate to high lipophilicity, and some degree of inhibition of AChE, a potential contributor to sulfur mustard-mediated tissue damage. Copyright © 2011 John Wiley & Sons, Ltd. |
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Authors:
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Sherri C Young; Karine M Fabio; Mou-Tuan Huang; Jaya Saxena; Meredith P Harman; Christophe D Guillon; Anna M Vetrano; Diane E Heck; Robert A Flowers; Ned D Heindel; Jeffrey D Laskin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-11 |
Journal Detail:
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Title: Journal of applied toxicology : JAT Volume: - ISSN: 1099-1263 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109495 Medline TA: J Appl Toxicol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Chemistry, Lehigh University, Bethlehem, PA, 18015, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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